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Reduced kidney function and protein leaking into the urine may be warning signs for acute kidney injury, researchers warned.

Preexisting problems with glomerular filtration predicted up to seven-fold elevated risk of acute kidney injury, found Josef Coresh, MD, PhD, MHS, of the Johns Hopkins Bloomberg School of Public Health in Baltimore, and colleagues.

Macroalbuminuria nearly quintupled the risk of incident acute kidney injury, they reported online in the Journal of the American Society of Nephrology.

However, even subclinical albuminuria at baseline more than doubled the risk of incident acute kidney injury, the researchers noted.

"As therapy for acute kidney injury prevention is refined, preventative measures extended to high-risk groups (e.g., older persons and those with more advanced chronic kidney disease) should also be considered for those with albuminuria," Coresh's group wrote in the paper.

Since there is little beyond supportive care that can be done for acute kidney injury, prevention is an important goal to prevent the chronic or end-stage renal problems as well as mortality that can result from it, the researchers pointed out.

The researchers analyzed factors associated with acute kidney injury among a prospective cohort of 11,200 participants in the Atherosclerosis Risk in Communities (ARIC) study.

During eight years of follow-up on average, 356 individuals developed acute kidney injury associated with hospitalization, for an incidence of 4.0 first events per 1,000 person-years.

Acute kidney injury as a cause of hospitalization appeared less common as indicated by the incidence of hospitalization with acute kidney injury as the first discharge diagnosis (0.8 per 1,000 person-years). Dialysis was more common in these hospitalizations (23.2% versus 12.8% overall).

Overall, only 2.8% of hospitalizations in the cohort were associated with acute kidney injury, but these hospitalizations were substantially longer (14.6 versus 5.5 days) and associated with higher inhospital mortality rates (18.9% versus 2.5%).

Baseline renal disease predicted elevated risk of acute kidney injury. Once the eGFR fell below 75 ml/min per 1.73m², lower increments predicted significantly increased risk with urinary albumin-to-creatinine-adjusted hazard ratios of:

• 1.5 (95% CI 1.1 to 2.1) at an eGFR of 60 to 74 ml/min per 1.73m²
• 2.5 (95% CI 1.7 to 3.7) at an eGFR of 45 to 59 ml/min per 1.73m²
• 7.0 (95% CI 4.4 to 11.0) at an eGFR of 30 to 44 ml/min per 1.73m²
• 5.6 (95% CI 2.6 to 12.1) at an eGFR of 15 to 29 ml/min per 1.73m²

Greater baseline albuminuria also predicted greater risk of incident acute kidney injury, even at levels "below those typically considered pathologic" and below what a dipstick test would consistently detect, the researchers wrote in the paper.

The rate per 1,000 person-years rose from:

• 2.6 events with no albuminuria (10 mg/g or less urinary albumin-to-creatinine ratio)
• 6.0 events with subclinical albuminuria of 10 to 29 mg/g
• 11.1 events with microalbuminuria of 30 to 299 mg/g
• 41.2 events with macroalbuminuria of at least 300 mg/g

This apparently stepwise association persisted when controlling for categories of estimated glomerular filtration rate (eGFR) with odds ratios of 1.9 (95% CI 1.4 to 2.6), 2.2 (95% CI 1.6 to 3.0), and 4.8 (95% CI 3.2 to 7.2), respectively, compared with no albuminuria.

"This adds weight to the growing body of evidence that the presence of albuminuria should be considered a high-risk condition, and that this risk is in addition to any risk attributable to reduced eGFR," they wrote in the paper.

These associations remained in sensitivity analyses excluding open heart surgery and percutaneous coronary intervention hospitalizations -- known to increase kidney risk -- and adjusting for baseline use of ACE inhibitors and angiotensin-receptor blockers (ARBs).

The researchers cautioned that their study was limited by use of billing codes to identify acute kidney injury episodes, which likely missed many events.

Also, reliance on a single baseline measure of urinary albumin and creatinine ignored the random variation in these levels through the day, which may have led to underestimation of the true effect of renal function on acute kidney injury risk, they added.

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